Yeast of burden

An emerging species of Candida unlike any other is insidiously infecting hospitalized patients across the world.

Candida auris was first described in 2009, after it was isolated from a patient's external ear discharge
in Japan (hence the species name). But the yeast causes more than just ear infections.
In particular, candidemia is of paramount concern, with reported mortality rates as
high as 60%, based on data from a limited number of patients, according to the CDC.

Photo courtesy of the CDC

Beyond its reputation for high mortality, C. auris is also often resistant to multiple antifungal drugs, the CDC reported last November.
To make matters worse, the species is difficult to both identify and eradicate, said
Jose A. Vazquez, MD, FACP, a professor of medicine and chief of the division of infectious
diseases at the Medical College of Georgia at Augusta University. “It's like
one great perfect storm to really be able to have this organism be transmitted all
over the world,” he said.

In the U.S., the first known case of C. auris was discovered in 2013, and as of Feb. 16, 35 cases have been reported in five states.
The overwhelming majority of cases (28) were reported in New York, three were reported
in Illinois, two were reported in New Jersey, and one case each had been reported
in Maryland and Massachusetts, according to the CDC. C. auris infections have also occurred in South America, Asia, Europe, and Africa.

Experts offered five key points that hospitalists should know about this evolving
health threat.

1. Unlike other Candida species, C. auris is difficult to eradicate from the hospital environment.

C. auris does not seem to be acting like a typical, commensal Candida, said Tom Chiller, MD, MPHTM, chief of the CDC's Mycotic Diseases Branch. Instead,
it's behaving more like a nosocomial bacteria (e.g., Acinetobacter species, carbapenem-resistant Enterobacteriaceae) that sticks to surfaces and spreads
from surface to patient, health care worker to patient, or patient to patient, he
said. “Normally, [hospitalists] would see a Candida, and they're not going to be worried about contact precautions [or] spread to other
patients in the same room,” Dr. Chiller said.

However, clinicians must take a novel approach with this strange new pathogen. “We
need to take slightly different actions here and treat it more like a transmissible
bacteria that they're used to dealing with, take precautions in infection control,
and work with your micro[biology] lab to try to get a Candida species identified that is unidentifiable,” Dr. Chiller said.

At least in the U.S., C. auris appears to be a hospital phenomenon, and the CDC is not yet as worried about the yeast
spreading in the community, he added. It has caused outbreaks in health care facilities,
and one of the largest to date occurred in a thoracic ICU at a London hospital specializing
in cardiothoracic surgery. From April 2015 to July 2016, 50 cases of C. auris colonization were identified, with a 44% observed rate of infection and an 18% rate
of candidemia, according to a study published last October in Antimicrobial Resistance & Infection Control. The study authors noted that C. auris carriage was negligible in the admitted population and that no deaths were directly
attributable to the related infections.

Moreover, the study highlights the yeast's persistent presence around bed spaces,
equipment monitors, and other fomites. This demonstrates just how resilient and difficult
to eradicate C. auris can be, even in a sophisticated ICU, said Cornelius J. Clancy, MD, an associate professor
of medicine and director of the mycology program at the University of Pittsburgh School
of Medicine. “To me, probably the greatest threat that this presents is that
if it ends up getting into hospitals—even hospitals that have robust infection
control measures—from what we know to this point, it can be a very, very tough
thing to control,” he said.

2. C. auris has shown resistance to all three major classes of antifungals.

The yeast species has demonstrated the ability to become multidrug resistant, Dr.
Chiller said. “We have found some of these isolates to be—not in the
U.S. yet—resistant to all three classes. That's concerning,” he said.
In cases of such broad resistance, multiple antifungal classes at high doses may be
required to treat an infection, according to the CDC.

“This is the very first time that we have ever even considered having a yeast
that is multidrug resistant,” said Dr. Vazquez, a Candida researcher who participated in creating the CDC's interim recommendations last November
(see sidebar). He drew comparisons with the rapid global spread of multidrug-resistant
bacteria, such as those that produce Klebsiella pneumoniae carbapenemase or extended spectrum beta-lactamase. “A couple of isolates in
New York and a couple of isolates in London and Paris and, lo and behold, five or
six years later, it's all over the world,” Dr. Vazquez said.

To this point, most C. auris isolates that have been described throughout the world have been resistant to fluconazole,
and amphotericin B resistance rates appear to be in the 30% to 50% range, Dr. Clancy
said. With resistance rates around 10% in the studies reported thus far, echinocandins
appear to be the most viable treatment in the antifungal armamentarium, he said.

3. The most vulnerable patients are often the sickest.

Based on limited data, risk factors for C. auris infection seem to be similar to those for other types of Candida infections (e.g., recent surgery, diabetes, broad-spectrum antibiotic and antifungal
use, and central venous catheter use), according to the CDC. Infections have affected
patients of all ages and have most frequently occurred in patients hospitalized for
other reasons, according to the agency.

The first few C. auris infections in the U.S. have occurred in very sick, medically compromised patients
who have been in and out of health care facilities and received procedures and central
lines, Dr. Chiller said. “It is being found in the sickest of the sick, which
doesn't surprise me for a new organism that is trying to figure out its niche and
is, thankfully, just being barely introduced in this country,” he said. So
far, U.S. cases seem to be very localized. “I think that's good. I think we're
early in this emergence, and now is the time to act and to really try to contain as
best we can,” Dr. Chiller said.

4. Infection with C. auris may have higher mortality rates than other strains of Candida.

Despite aforementioned mortality rates hovering around 60%, it's unclear whether patients
with invasive C. auris infection are any more likely to die than those infected with other Candida species, Dr. Chiller said. “Mortality with patients in these populations that
are very sick in ICUs is always a challenge to attribute to one thing. . . . We need
more data to understand the true attributable mortality,” he said.

Dr. Clancy said he believes that as more cases of C. auris get reported, the 60% figure will likely be the upper limit of mortality for severe
bloodstream infections. “My guess is that overall mortality is going to be
comparable to what we see with Candida bloodstream infections due to Candida albicans or other species that we already encounter, which are already pretty high—usually
in the range of about 40% overall,” he said.

5. Most hospital laboratories won't be able to correctly identify C. auris.

C. auris is not readily identified by biochemical techniques or by the machines used in hospitals
to identify organisms, Dr. Chiller said. Most hospitals test bloodstream isolates
down to the species level, but C. auris frequently masquerades as other Candida species, said Dr. Clancy, who is also chief of the infectious diseases section at
the Veterans Affairs Pittsburgh Health Care System. “I think the key thing
for hospitalists, and for all providers, at this stage of the game is to understand
how your lab is doing testing, how it's identifying Candida species, and if it has methods that would detect C. auris or not,” he said.

Labs that are equipped to correctly identify the yeast employ matrix-assisted laser
desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry testing with a
library that contains C. auris sequences or direct DNA sequencing, Dr. Clancy said. More commonly used conventional
methods get it wrong. For example, the API 20C system might misidentify C. auris as Rhodotorula glutinis, the VITEK 2 method could pick up C. haemulonii, and the MicroScan method could produce various results (e.g., C. famata), he said.

If any of these unusual yeast species are detected in the blood or if a patient is
not responding to conventional antifungal therapy, clinicians may consider submitting
the isolate to the CDC to see if C. auris is the culprit, said Dr. Vazquez. “I would say 99% of institutions have no
way of knowing they even have a C. auris infection,” he said.

Current CDC recommendations

The CDC in November released a set of interim recommendations for diagnosing and treating Candida auris, as well as for infection control measures. The full recommendations, which will
continue to be updated, are summarized below and are available online.

Laboratory diagnosis: Traditional biochemical methods for yeast identification can misidentify C. auris as a different organism or “Candida spp.” The yeast should be suspected when an isolate is identified as C. haemulonii, C. famata, C. sake, Saccharomyces cerevisiae, or Rhodotorula glutinis, and in cases of antifungal resistance among these species.

Treatment: Based on the limited data available, an echinocandin is the recommended initial therapy
to treat C. auris infections. The following drugs are recommended: anidulafungin (loading dose 200 mg,
then 100 mg daily), caspofungin (loading dose 70 mg, then 50 mg daily), or micafungin
(100 mg daily). If the patient is clinically unresponsive to echinocandin treatment
or has persistent fungemia for more than five days, clinicians could consider switching
to a lipid formulation of amphotericin B (3 to 5 mg/kg daily). In general, treatment
is only indicated if clinical disease is present, and consultation of an infectious
disease subspecialist is highly recommended.

Infection control measures: In acute care settings, clinicians should place patients with C. auris infection or colonization in single rooms on standard and contact precautions. Facilities
should ensure daily terminal cleaning and disinfection of these rooms using an Environmental
Protection Agency-registered hospital-grade disinfectant effective against Clostridium
difficile spores.

Reporting: Clinicians who suspect they have a patient with C. auris infection should contact state or local public health authorities and the CDC.

ACP Hospitalist provides news and information for hospitalists, covering the major issues in the field. All published material, which is covered by copyright, represents the views of the contributor and does not reflect the opinion of the American College of Physicians or any other institution unless clearly stated.